Glucagon-like peptide-1 counteracts oxidative stress-dependent apoptosis of human cardiac progenitor cells by inhibiting the activation of the c-Jun N-terminal protein kinase signaling pathway.

Increased apoptosis of cardiac progenitor cells (CPCs) has been proposed as a mechanism of myocardial damage and dysfunction. Glucagon-like peptide-1 (GLP-1) has been shown to improve heart recovery and function after ischemia and to promote cell survival. The protective effects of GLP-1 on oxidative stress-induced apoptosis were investigated in human CPCs isolated from human heart biopsies. Mesenchymal-type cells were isolated from human heart biopsies, exhibited the marker profile of CPCs, differentiated toward the myocardiocyte, adipocyte, chondrocyte, and osteocyte lineages under appropriate culture conditions, and expressed functional GLP-1 receptors. CPCs were incubated with GLP-1 with or without hydrogen peroxide (H(2)O(2)). Phospho- and total proteins were detected by immunoblotting and immunofluorescence analysis. Gene expression was evaluated by quantitative RT-PCR. The role of the canonical GLP-1 receptor was assessed by using the receptor antagonist exendin(9-39) and receptor-specific silencer small interfering RNAs. Cell apoptosis was quantified by an ELISA assay and by flow cytometry-detected Annexin V. Exposure of CPCs to H(2)O(2) induced a 2-fold increase in cell apoptosis, mediated by activation of the c-Jun N-terminal protein kinase (JNK) pathway. Preincubation of CPCs with GLP-1 avoided H(2)O(2)-triggered JNK phosphorylation and nuclear localization, and protected CPCs from apoptosis. The GLP-1 effects were markedly reduced by coincubation with the receptor antagonist exendin(9-39), small interfering RNA-mediated silencing of the GLP-1 receptor, and pretreatment with the protein kinase A inhibitor H89. In conclusion, activation of GLP-1 receptors prevents oxidative stress-mediated apoptosis in human CPCs by interfering with JNK activation and may represent an important mechanism for the cardioprotective effects of GLP-1.

Primary plasmacytoma of the cervix in a 21-year-old female patient.

Extramedullary (extraosseous) plasmacytomas are localized, plasma cell neoplasms that arise in tissues other than bone and bone marrow, and constitute about 4% of all plasma cell neoplasms. Extramedullary (extraosseous) plasmacytomas rarely affects the female lower genital tract; only 6 cases of primary cervix plasmacytomas have been reported to date. Here we describe the case of an otherwise healthy 21-year-old woman who presented for a routine examination with no symptoms. A Pap smear showed an intense inflammatory process with some atypical cells. This was confirmed by microscopic examination of a biopsy, which revealed a metaplastic process of the cervix with a massive infiltration of plasma cells with mild atypia. The atypical plasma cells showed cytoplasmic lambda immunoglobulin light chain restriction with the absence of kappa light chains, indicative of monoclonality. The patient was extensively screened for systemic disease, including bone marrow biopsy, but the disease was restricted to the cervix.

Melkersson-Rosenthal syndrome.

Melkersson-Rosenthal syndrome is a rare condition, classically associated with a triad of facial and/or lip edema, fissured tongue, and relapsing facial palsy. This article offers a review of the literature and presents two cases of Melkersson-Rosenthal syndrome associated with elevated serum levels of angiotensin converting enzyme in two patients of Thai descent.